Primecuts – This Week In The Journals

December 3, 2013

By Matthew Lee, MD

Peer Reviewed

Thanksgiving has traditionally been characterized by turkey-centric meals and Black Friday madness, but these phenomena were joined this year by both NCAA football’s rivalry week and Thanksgivukkah (the alignment of Thanksgiving and first day of Hanukkah). While people took time off to celebrate the holiday festivities, the medical journal world continued to turn, bringing us to this week’s articles.

Our first article by Mulder et al. [1] looks at glucose management in patients admitted for acute coronary syndrome (ACS). Prior studies found that elevated glucose levels at admission were associated with an increased risk of mortality in both diabetic and non-diabetic patients [2]. Follow-up studies on glucose control and its effect on mortality and morbidity have revealed conflicting results. In this open-label randomized study, Mulder et al. evaluated whether glucose control could limit infarct size. The primary outcome of the study was median troponin level after 72 hours with secondary outcomes consisting of the area under the curve of CK-MB levels, perfusion imaging at six weeks, and a composite of all-cause death and second nonfatal myocardial infarction (MI). Patients admitted with ACS were randomized to either “intensive” (goal FSG < 140 through use of IV insulin) or “conventional” (goal < 288) groups.

No statistical difference in the primary and most secondary endpoints was found 72 hours after admission, with the authors concluding that intensive glucose control does not limit infarct size. There were significant potential flaws in the methodology of the study including delays in insulin initiation (often hours post-intervention) and the exclusion of insulin-dependent diabetics. In addition, the authors noted that there was an increase in the composite end-point of death or second spontaneous MI in those receiving intensive glucose control, yet conclusions are difficult to draw from this secondary outcome.

Continuing with the diabetes theme, a new study by Huang et al. [3] investigated the effect of new onset of diabetes in chronic hepatitis B patients and the risk of progression to cirrhosis. This Taiwanese cohort study followed roughly 8000 non-cirrhotic, hepatitis B patients over a 9-year period. Outcomes were compared between those receiving a new diagnosis of diabetes (n=351) versus non-diabetics (n=7886). Noteworthy exclusion criteria were any previous diagnoses of varices, hepatitis C, primary biliary cirrhosis, or alcoholic liver disease in order to minimize cirrhotic risk factors. At the end of the study, the diabetic cohort had both an elevated risk of new onset cirrhosis (relative risk [RR] 3.43, 95% CI, 2.62-4.49; absolute risk increase of 8.2%) and hepatocellular carcinoma (absloute risk increase of 3.5%) when compared to the non-diabetic cohort. In addition, diabetic patients were found to be at higher risk for developing decompensated cirrhosis (RR 4.11, 95% CI, 2.95-5.70). When controlling for clinical characteristics (including age, co-morbidities, and hepatitis B treatment), the study also found diabetes to be an independent predictor for cirrhosis development (hazard ratio 1.792, 95% CI, 1.192-2.695). These findings provide initial evidence that the development of diabetes in hepatitis B patients can accelerate the progression to cirrhosis. This study highlights an important preventative measure already in place: diabetic screening in hepatitis B patients, which stands in juxtaposition to the CDC recommendation for all diabetics under 60 to receive the hepatitis B vaccine [4]. Further investigation into whether tight glucose control could change disease progression of hepatitis B is also warranted.

Lastly, Starling et al. [5] reported on an increasing rate of left ventricular assist device (LVAD) thrombosis observed from March 2011 to January 2013. Initial post-approval studies prior to 2011 had reported an LVAD thrombosis rate up to 4% [6]. However, single-center reports of higher incidence rates led to this multi-center, observational study. The primary end-point was confirmed pump thrombosis (defined as thrombus found on the blood-contacting surfaces of the HeartMate II, its inflow cannula, or its outflow conduit at pump replacement, urgent transplantation, or autopsy) with secondary end-points including clinically suspected thrombosis, LDH levels (indicating hemolysis), and outcomes of thrombosis management. The study found that the incidence of thrombosis 3 months post-implantation increased from 2.2% (95% CI, 1.5-3.4) in March 2011 to 8.4% (95% CI, 5.0-13.9) in January 2013. There was also a notable decrease in time from implantation to thrombosis of 18.6 months (95% CI, 0.5-52.7) to 2.7 months (95% CI, 0.0-18.6) over the same time period. LDH levels were notable for a near 3-fold increase over 6 weeks prior to thrombosis. Strikingly, patients with thrombosis who were not treated with urgent heart transplantation or device replacement had a mortality of 48.2% (95% CI, 31.6-65.2) at 6 months. The reason behind the increased thrombosis rate remains unknown, but is likely multifactorial in nature. It remains unclear how management decisions will be impacted in light of this new information.

Other notable articles include:

A study from JAMA looked at the relationship between physician’s diagnostic accuracy and confidence. Physicians were presented with “easy” and “difficult” clinical cases and then asked about their confidence level on a scale from 0-10. Despite maintaining confidence levels of 6-7/10, only 5.8% of physicians were able to correctly diagnose the “difficult” cases. This discordance between correct diagnosis and confidence level highlights the need to maintain an ability to “step back” and re-evaluate, particularly in challenging cases.

An article in the NEJM presented data from a large, pharmaceutical-funded, randomized, double blind non-inferiority trial comparing low-dose (30 mg daily) or high-dose (60 mg daily) edoxaban (a direct Xa inhibitor; trade name Lixiana) to warfarin. Both low and high-dose edoxaban were found to be non-inferior in regards to primary end points (stroke or systemic embolic events) with edoxaban also found to have lower major adverse bleeding events. The study presented supportive data for yet another oral anti-coagulant and highlighted the potential for a decrease in bleeding outcomes with this novel agent.

4. Centers for Disease Control and Prevention. Use of hepatitis B vaccination for adults with diabetes mellitus: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR. 2011;60(50):1709-1711. http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6050a4.htm

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